Biological Processes and Biomarkers Related to Frailty in Older Adults: A State-of-the-Science Literature Review

The objectives of this literature review were to (1) synthesize biological processes linked to frailty and their corresponding biomarkers and (2) identify potential associations among these processes and biomarkers. In September 2016, PubMed, Cumulative Index to Nursing and Allied Health, Cochrane Library, and Embase were searched. Studies examining biological processes related to frailty in older adults (≥60 years) were included. Studies were excluded if they did not employ specific measures of frailty, did not report the association between biomarkers and frailty, or focused on nonelderly samples (average age < 60). Review articles, commentaries, editorials, and non-English articles were also excluded. Fifty-two articles were reviewed, reporting six biological processes related to frailty and multiple associated biomarkers. The processes (biomarkers) include brain changes (neurotrophic factor, gray matter volume), endocrine dysregulation (growth hormones [insulin-like growth factor-1 and binding proteins], hormones related to glucose and insulin, the vitamin D axis, thyroid function, reproductive axis, and hypothalamic-pituitary-adrenal axis), enhanced inflammation (C-reactive protein, interleukin-6), immune dysfunction (neutrophils, monocytes, neopterin, CD8+CD28-T cells, albumin), metabolic imbalance (micronutrients, metabolites, enzyme-activity indices, metabolic end products), and oxidative stress (antioxidants, telomere length, glutathione/oxidized glutathione ratio). Bidirectional interrelationships exist within and between these processes. Biomarkers were associated with frailty in varied strengths, and the causality remains unclear. In conclusion, frailty is related to multisystem physiological changes. Future research should examine the dynamic interactions among these processes to inform causality of frailty. Given the multifactorial nature of frailty, a composite index of multisystem biomarkers would likely be more informative than single biomarkers in early detection of frailty.